Lehrer R I, Lichtenstein A K, Ganz T
Department of Medicine, University of California, Los Angeles 90024.
Annu Rev Immunol. 1993;11:105-28. doi: 10.1146/annurev.iy.11.040193.000541.
Defensins are antimicrobial and cytotoxic peptides that contain 29-35 amino acid residues, including six invariant cysteines whose intramolecular disulfide bonds cyclize and stabilize them in a complexly folded, triple-stranded beta-sheet configuration. Generated by the proteolytic processing of 93-95 amino acid precursor peptides, the constitute > 5% of the total cellular protein in human and rabbit neutrophils (polymorphonucleated neutrophils--PMN) and are also produced by rabbit lung macrophages and by mouse and rabbit small intestinal Paneth cells. Despite their prominence in rat PMN, defensins are not found in murine PMN. The antimicrobial spectrum of defensins includes gram positive and gram negative bacteria, mycobacteria, T. pallidum, many fungi, and some enveloped viruses. Defensins exert nonspecific cytotoxic activity against a wide range of normal and malignant targets, including cells resistant to TNF-alpha and NK-cytolytic factor. They appear to kill mammalian target cells and microorganisms by a common mechanism, which involves initial electrostatic interactions with negatively charged target cell surface molecules (likely the head groups of polar membrane lipids), followed by insertion into the cell membranes which they permeabilize, forming voltage-regulated channels. In addition to their antimicrobial and cytotoxic properties, some defensins act as opsonins, while others inhibit protein kinase C, bind specifically to the ACTH receptor and block steroidogenesis or act as selective chemoattractants for monocytes. Defensins are a newly delineated family of effector molecules whose contribution to host defense, inflammation, and cytotoxicity may be considerable for humans, even though it is unlikely to be revealed by experimentation with mice.
防御素是一类抗菌和具有细胞毒性的肽，含有29 - 35个氨基酸残基，包括6个不变的半胱氨酸，其分子内二硫键使肽环化并稳定在复杂折叠的三链β - 折叠结构中。它们由93 - 95个氨基酸的前体肽经蛋白水解加工产生，在人和兔的中性粒细胞（多形核中性粒细胞——PMN）中占细胞总蛋白的5%以上，兔肺巨噬细胞以及小鼠和兔的小肠潘氏细胞也能产生防御素。尽管防御素在大鼠PMN中很突出，但在小鼠PMN中未发现。防御素的抗菌谱包括革兰氏阳性菌和革兰氏阴性菌、分枝杆菌、梅毒螺旋体、许多真菌以及一些包膜病毒。防御素对多种正常和恶性靶标具有非特异性细胞毒性活性，包括对TNF -α和NK细胞溶解因子有抗性的细胞。它们似乎通过一种共同机制杀死哺乳动物靶细胞和微生物，该机制涉及最初与带负电荷的靶细胞表面分子（可能是极性膜脂的头部基团）的静电相互作用，随后插入细胞膜并使其通透化，形成电压调节通道。除了抗菌和细胞毒性特性外，一些防御素还可作为调理素，而另一些则抑制蛋白激酶C、特异性结合促肾上腺皮质激素受体并阻断类固醇生成，或作为单核细胞的选择性趋化因子。防御素是一类新划定的效应分子家族，它们对人类宿主防御、炎症和细胞毒性的贡献可能相当大，尽管通过小鼠实验不太可能揭示这一点。
